Mechanism of Aging

Question 1

Define aging

Answer 1

failure to maintain homeostasis under conditions of physiological stress accompanied by a decreased viability and increased vulnerability of the individual

Question 2

True or false? aging is the most important risk for most chronic diseases

Answer 2

true

Question 3

This is a group of effects which lead to a decreasing expectation of life with increasing age

Answer 3

senescence

Question 4

In recent history, the documented age of human has not exceeded ____ years, which means it’s probably an upper limit for natural aging

Answer 4

122

Question 5

Studies have suggested that life-span is determined ___-___% by genetics

Answer 5

30-35

Question 6

Organisms as diverse as fruit flies and monkeys when placed on calorie restricted diets show up to a ___% increase in maximum life spans

Answer 6

50

Question 7

The ____-__ mutant of C. elegant has maximum life-span increased by 100% due to having a slower metabolism

Answer 7

age-1 (single gene mutation in PI3 Kinase homolog)

Question 8

In mice, caloric restriction coupled with an insulin/IGF pathway mutation can ____ lifespan

Answer 8

double

Question 9

Fibroblasts having a limited proliferative capacity in vitro of about 50 population doublings is known as the ____ limit

Answer 9

Hayflick

Question 10

Describe the error or “wear and tear” hypothesis of aging

Answer 10

damage to cellular structure eventually leads to cell death

Question 11

Describe the programmed cell death hypothesis of aging

Answer 11

senescence inducing genes limit life span of cells

Question 12

A strong correlation exits between metabolic rate and rate of aging in certain species. Cold blooded species show ____ life span when metabolic rate is decreased by temperature

Answer 12

increased

Question 13

In regards to waste product accumulation, this is non-enzymatic glycosylation of long lived proteins which leads to oxidized, cross linked products which accumulate within cells as they age.

Answer 13

lipofuscin

Question 14

Damage to DNA accumulates with age due to inadequate DNA repair processing with age. This increases the incidence of _____

Answer 14

cancer

Question 15

Free radicals have been thought to be correlated with aging. Where are most free radicals generated?

Answer 15

mitochondria

note: cellular functional impairment occurs when oxygen radicals overwhelm natural cellular antioxidant defenses

Question 16

True or false? current evidence supports anti-oxidant supplementation as a major means to prevent age-related pathology

Answer 16

false; it does NOT support this

Question 17

This is the enzyme responsible for synthesizing telomeres. This enzyme is present in the germ cell line, but not somatic cells

Answer 17

telomerase

Question 18

Overexpression of telomerase in mice increases lifespan, but only in ____-resistant mice

Answer 18

cancer

Question 19

Oxidative phosphorylation declines with age. True or false?

Answer 19

true - mitochondria function declines with age

Question 20

Overexpression of mitochondrial catalase in mice leads to a 20% _____ in maximum life span

Answer 20

increase

note: supports mitochondrial function (oxidative phosphorylation)

Question 21

Autophagy - cellular self-digestion (supply nutrients and remove damaged proteins) ____ with aging

Answer 21

declines

Question 22

Proponents of this hypothesis say aging is just an extension of the developmental program - a death program that kicks in during the post-reproductive years

Answer 22

program hypothesis

Question 23

What is the problem with the program hypothesis?

Answer 23

there can be no genetic selective advantage to decreased or increased lifespan for post-reproductive age

Question 24

What mutation causes Werner’s syndrome and how does it present?

Answer 24

mutation: DNA helicase
symptoms: gray hair before 27, bilateral cataracts, osteoporosis, death by late 40’s

Question 25

What mutation causes Hutchison-Gilford Progeria Syndrome and how does it present?

Answer 25

mutation: lamin A - nuclear structural gene involved in chromosome maintenance/DNA repair
symptoms: stroke or heart attack by 13, children resemble aging traits of an 80 yo

Question 26

_____ is produced in the liver in response to growth hormone secretion from the pituitary gland It activates a signaling pathway that inactivates FoxO TFs

Answer 26

IGF-1

Question 27

IGF-1 mutants seem to be linked to protection of mitochondria from ____ ____

Answer 27

oxidative damage

Question 28

_____ is a major complex of proteins which monitors nutrients and stress in the cell

Answer 28

TOR

Question 29

TOR kinase regulates proteins synthesis in the cell in response to stress and nutrient levels. TOR kinase inhibition is linked to what?

Answer 29

increased longevity

Question 30

AMP kinase is a nutrient and energy sensor that represses ____ pathways when the cell’s AMP/ATP ratio rises

Answer 30

anabolic

Question 31

AMP kinase acts on _____ TF’s which regulate energy metabolism and longevity

Answer 31

FoxO

Question 32

_____ activates AMP kinase and can extend lifespan in mice

Answer 32

Metformin

Question 33

This group of proteins are linked to regulation of metabolism due to the fact that they have NAD-dependent deacetylase activity. They regulate genes linked to switches in metabolism and their activity changes during aging.

Answer 33

Sirtuins

Question 34

Humans have ___ SIRT genes

Answer 34

7

Question 35

SIRT 1 is linked to what?

Answer 35

IGF-1, autophagy, and mitochondria biosynthesis

Question 36

Chronic inflammation plays a role in the progression of age related diseases. ____ cells secrete interleukins

Answer 36

Senescent

Question 37

Which vitamin has multiple anti-aging qualities?

Answer 37

Vitamin D